Travoprost Intracameral Implant for Open-Angle Glaucoma or Ocular Hypertension: 12-Month Results of a Randomized, Double-Masked Trial

Abstract

Introduction: This prospective, multicenter, randomized, double-masked pivotal phase 3 trial evaluated the efficacy and safety of the travoprost intracameral SE-implant (slow-eluting implant, the intended commercial product) and FE-implant (fast-eluting implant, included primarily for masking purposes) compared to twice-daily (BID) timolol ophthalmic solution, 0.5% in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).

Methods: The trial enrolled adult patients with OAG or OHT with an unmedicated mean diurnal intraocular pressure (IOP) of ≥ 21 and unmedicated IOP ≤ 36 mmHg at each diurnal timepoint (8 A.M., 10 A.M., and 4 P.M.) at baseline. The eligible eye of each patient was administered an SE-implant, an FE-implant or had a sham administration procedure. Patients who received an implant were provided placebo eye drops to be administered BID and patients who had the sham procedure were provided timolol eye drops to be administered BID. The primary efficacy endpoint, for which the study was powered, was mean change from baseline IOP at 8 A.M. and 10 A.M. at day 10, week 6, and month 3. Non-inferiority was achieved if the upper 95% confidence interval (CI) on the difference in IOP change from baseline (implant minus timolol) was < 1.5 mmHg at all six timepoints and < 1 mmHg at three or more timepoints. The key secondary endpoint was mean change from baseline IOP at 8 A.M. and 10 A.M. at month 12. Non-inferiority at month 12 was achieved if the upper 95% CI was < 1.5 mmHg at both timepoints. Safety outcomes included treatment-emergent adverse events (TEAEs) and ophthalmic assessments.

Results: A total of 590 patients were enrolled at 45 sites and randomized to one of three treatment groups: 197 SE-implant (the intended commercial product), 200 FE-implant, and 193 timolol. The SE-implant was non-inferior to timolol eye drops in IOP lowering over the first 3 months, and was also non-inferior to timolol at months 6, 9, and 12. The FE-implant was non-inferior to timolol over the first 3 months, and also at months 6 and 9. Of those patients who were on glaucoma medication at screening, a significantly greater proportion of patients in the SE- and FE-implant groups (83.5% and 78.7%, respectively) compared to the timolol group (23.9%) were on fewer topical glaucoma medications at month 12 compared to screening (P < 0.0001, chi-square test). TEAEs, mostly mild, were reported in the study eyes of 39.5% of patients in the SE-implant group, 34.0% of patients in the FE-implant group and 20.1% of patients in the timolol group.

Conclusions: The SE-travoprost intracameral implant demonstrated non-inferiority to timolol over 12 months whereas the FE-implant demonstrated non-inferiority over 9 months. Both implant models were safe and effective in IOP lowering in patients with OAG or OHT.

Trial registration: ClinicalTrials.gov identifier, NCT03519386.

Keywords: Intraocular pressure; Ocular drug delivery system; Ocular hypertension; Open-angle glaucoma; Travoprost intracameral implant; iDose® TR.

Fig. 1

Gonioscopic view of a travoprost intracameral implant anchored in the trabecular meshwork and sclera just anterior to the scleral spur, and oriented parallel to the iris

Fig. 2

LS mean change from baseline in IOP at the 8 a.m. and 10 a.m. measurement timepoints at day 10, week 6, month 3 and month 12, and at the 8 a.m., 10 a.m., or 4 p.m. measurement timepoint at month 6 and 9. Data below the plot indicate the LS means difference and upper and lower 95% CIs in the IOP change from baseline (in mmHg) between the implant group and the timolol group at each timepoint and visit. CIs confidence intervals, FE-implant fast-eluting travoprost intracameral implant, IOP intraocular pressure, LS mean least squares mean, SE-implant slow-eluting travoprost intracameral implant

Fig. 3

The proportion of patients who did not require additional topical glaucoma medications was similar in the SE-implant group and in the FE-implant group compared to the timolol group at each visit (P > 0.05, Fisher’s exact test). FE-implant fast-eluting travoprost intracameral implant, SE-implant slow-eluting travoprost intracameral implant

Fig. 4

The proportion of patients on the same or fewer topical glaucoma medications (at left) and of those who were on glaucoma medication at screening, the proportion of patients who were on fewer topical glaucoma medications (at right) at month 12 compared to screening. In both analyses, the proportion of patients in the SE-implant group and in the FE-implant group was significantly greater than the proportion of patients in the timolol group (*P < 0.0001, chi-square test comparing each implant group to timolol). FE-implant fast-eluting travoprost intracameral implant, SE-implant slow-eluting travoprost intracameral implant

Fig. 5

Mean (+ SD) central corneal endothelial cell density at baseline, month 3, and month 12. FE-implant fast-eluting travoprost intracameral implant, SD standard deviation, SE-implant slow-eluting travoprost intracameral implant

Fig. 6

Best corrected visual acuity (number of ETDRS letters, + SD) at baseline, weeks 4 and 6, and months 3, 6, 9, and 12. ETDRS Early Treatment Diabetic Retinopathy Study, FE-implant fast-eluting travoprost intracameral implant, SD standard deviation, SE-implant slow-eluting travoprost intracameral implant

Fig. 7

Mean conjunctival hyperemia score (+ SD) at baseline, and each post-baseline visit. Conjunctival hyperemia was measured at the slit-lamp against a photographic scale with grades of 0 (normal), 0.5 (trace), 1 (mild), 2 (moderate), and 3 (severe). FE-implant fast-eluting travoprost intracameral implant, SD standard deviation, SE-implant slow-eluting travoprost intracameral implant